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Endogenous LRRK2 dimerizes and translocates to novel membrane compartments during monocyte activation
Author(s) -
Schapansky Jason,
LaVoie Matthew J
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.873.17
Subject(s) - lrrk2 , microbiology and biotechnology , kinase , monocyte , phosphorylation , compartment (ship) , chemistry , membrane , function (biology) , cellular compartment , biology , cell , biochemistry , mutation , immunology , gene , oceanography , geology
Mutations in leucine‐rich repeat kinase 2 (LRRK2) are the most common genetic cause of Parkinson's disease (PD), and recent evidence indicates LRRK2 also plays a significant role in monocyte immune cell function. Our previous research indicated that membrane‐associated LRRK2 dimers are likely the more physiologically relevant species, but the function and action of this post‐translational modification was unknown. Here, we demonstrate activation of macrophage or microglial cell lines results in LRRK2 phosphorylation and dimerization, which then coincided with iNOS expression and nitrate production. This activation also resulted in localization to a novel membrane compartment different from basal membrane LRRK2. Disruption of LRRK2 kinase activity, or dimerization with 2BP, prevented iNOS expression and activity. This research shows that, for the first time, acute changes in dimerization and membrane localization of endogenous LRRK2 for cellular function. This project was funded by the Michael J. Fox Foundation and NIH #NS072604.